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    Home > Medical News > Medical Research Articles > One thing drops one thing!

    One thing drops one thing!

    • Last Update: 2021-07-25
    • Source: Internet
    • Author: User
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    TP53 is a key tumor suppressor gene
    , which is usually inactivated by missense mutations in the DNA binding domain.
    These missense mutations usually make p53 lose its tumor suppressor activity, and at the same time produce a mutant p53 that can promote tumor progression (mtp53).
    ) Protein

    .
    The presence of mtp53 can increase chromosome instability, leading to the loss of tumor suppressor genes and the amplification of oncogenes

    .


    Recently, researchers from the Luis A Martinez project of Stony Brook University in the United States
    published a study titled Mutant p53 suppresses innate immune signaling to promote tumorigenesis in
    Cancer Cell , and found that mtp53 can inhibit innate immune signaling, thereby Causes immunity to escape .
    Restoring TBK1 signal can bypass mtp53 and restore the function of immune cells, eradicating cancer cells .



    To determine whether mtp53 regulates innate immune signaling pathways, the researchers first down-regulated the expression of mtp53 in human breast cancer cells BT549 (p53R249S), MDA-MB-231 (p53R280K) and pancreatic cell lines MIA PaCa

    .
    The results show that knocking down mtp53 can promote the phosphorylation of TBK1 and its substrates IRF3 and STING, which produce similar phenomena in both mouse and human cells

    .
    Moreover, in two different types of normal human fibroblasts, IMR-90 and human foreskin fibroblasts, overexpression of mtp53 can reduce the phosphorylation of TBK1 and its substrates IRF3 and STING

    .
    These results indicate that
    mtp53 blocks the activity of innate immune signaling pathways
    .


    In the tumor microenvironment, the TBK1/STING/IRF3 pathway signals the presence of tumor cells to immune cells

    .
    Researchers have found that
    mtp53 can block the nuclear translocation of IRF3, inhibit the innate immune response of cells in the cGAS/STING/TBK1/IRF3 pathway, and thereby inhibit IRF3-induced apoptosis
    .
    Mtp53 can also interfere with the formation of the TBK1-STING-IRF3 complex, which can inhibit immune surveillance in a host with an intact immune system, thereby accelerating tumor growth

    .
    Knockdown of mtp53 can promote the infiltration of CD3+, CD4+, CD8+ cells and NK cells

    .


    Interestingly, the researchers found that
    activating TBK1 can inhibit mtp53-induced tumor growth and restore immune surveillance
    .
    In other words, mtp53 induces inactivation of innate immune signals, changes the production of cytokines, and leads to immune escape; however,
    restoring TBK1 signals is sufficient to bypass mtp53, thereby restoring immune cell function and eradicating cancer cells
    .


    In general, the study found a new mechanism.
    Mtp53 inhibits cell-autonomous and non-cell signaling by interfering with the function of the cytoplasmic DNA sensing mechanism cGAS-STING-TBK1-IRF3, thereby promoting cancer cell growth and evading immune surveillance.

    .
    Restoring TBK1 signal can bypass mtp53, restore immune cell function, activate immune surveillance, and eradicate cancer cells

    .
    This is of great significance.
    The status of p53 can guide treatment and provide new therapeutic targets

    .

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